The lymphatic vasculature represents a second circulation, parallel to the blood vasculature, that accounts for the clearance of interstitial fluid (ISF) with its constituent proteins and other solutes not absorbed across postcapillary venules. In most vascularized tissues, the lymphatic system is critical to both hydrostatic and homeostatic maintenance. Yet, the brain does not have histologically identifiable lymphatic vessels and thus lacks the discrete pathways for interstitial solute and fluid clearance present in other peripheral tissues. This is surprising, because the high metabolic rate and exquisite sensitivity of neurons and glia to alterations in their extracellular environment suggest a need for rapid clearance of ISF and solutes.
The cerebrospinal fluid (CSF) of the central nervous system (CNS) has been thought to play a role in solute clearance from the brain. CSF formed in the choroid plexi flows through the cerebral ventricles and the subarachnoid space to its ultimate sites of reabsorption into the bloodstream via arachnoid villi of the dural sinuses, along cranial nerve sheaths or through the nasal lymphatics. Interstitial solutes have been thought to be cleared to the CSF by the convective bulk flow of ISF, which courses diffusely through brain tissue, rather than through an anatomically or functionally discrete structure.
Accumulation of toxic dysfunctional proteins in the mammalian central nervous system, including the brain and spinal cord, is associated with many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS) in humans. However, the mechanism that leads to the accumulation of toxins in the aging mammalian brain is not completely known. In the case of Alzheimer's disease (AD) two hallmarks are senile plaques, which are extracellular deposits of amyloid β (also referred to herein as amyloid-β, amyloid beta or Aβ) toxins, and intracellular neurofibrillary tangles (hyperphosphorylated tau). The “amyloid cascade” hypothesis suggests that the cognitive decline and the distinct pathogenic features in AD are related to abnormal accumulation of these toxins (Selkoe, D. J. “Clearing the Brain's Amyloid Cobwebs.” Neuron 32, no. 2 (2001): 177-80; Hardy, J. “A Hundred Years of Alzheimer's Disease Research.” Neuron 52, no. 1 (2006): 3-13).
U.S. Pat. No. 6,689,085 (Rubenstein et al. Feb. 10, 2004) discloses a method and apparatus for treating adult-onset dementia of the Alzheimer's type. According to the method, a portion of the patient's cerebrospinal fluid (CSF) is removed, by transporting the fluid to another portion of the patient's body. Also disclosed in U.S. Pat. No. 6,689,085 is a shunt for removing CSF.
Citation or identification of any reference in Section 2, or in any other section of this application, shall not be considered an admission that such reference is available as prior art to the present invention.